VB6-845 is a recombinantly expressed therapeutic protein consisting of a monoclonal antibody specific for the cell surface protein EpCAM linked to a modified form of bouganin (WO 2005/090579 A1). VB6-845 is currently being produced using an E. coli based recombinant protein expression system.
This product and other Fab-bouganin fusion proteins are intended for systemic administration and it is expected that patients would receive around 0.1-1.0 grams of protein per dose of treatment. Under this regimen it was found that that it would be economically advantageous to modify the existing expression system which typically yielded less than 1-10 mg/L, in order to increase product yield.
During recombinant protein production in a heterologous system improper folding of the nascent protein is often the cause of decreased yield of functional protein. Different approaches have been taken to improve folding and expression, including the use of chaperons, changes to the fermentation conditions to affect rate of production and various forms of re-engineering of the expression vector. (Vasseur-Godbillon et al., 2006; Endo et al., 2006; Xu et al., 2005; Makrides, 1996; Baneyx et al., 1991).